Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma release_mccuihchxzgvxg3u4ciksk5myu

by Ilse G C Hermsen, Harm R Haak, Ronald R de Krijger, Thomas M A Kerkhofs, Richard A Feelders, Wouter W de Herder, Hanneke Wilmink, Jan W A Smit, Hans Gelderblom, Noel F C C de Miranda, Ronald van Eijk, Tom van Wezel (+1 others)

Published in European Journal of Endocrinology by Bioscientifica.

2013   Volume 169, p51-58

Abstract

<jats:sec><jats:title>Background</jats:title>Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options. Mitotane is considered the standard first-line therapy with only 30% of the patients showing objective tumour response. Defining predictive factors for response is therefore of clinical importance. The epidermal growth factor receptor (EGFR) has been implicated in the development of one-third of all malignancies. EGFR pathway members in ACC have been investigated, however, without available clinical data and relation to survival.</jats:sec><jats:sec><jats:title>Methods</jats:title>In this study, mutation status of EGFR and downstream signalling pathways was evaluated in 47 ACC patients on mitotane using direct sequencing, a TaqMan allele-specific assay and immunohistochemistry. Archival formalin-fixed paraffin-embedded tumour tissue was used for all analyses. Patient data were obtained anonymously, after coupling with the collected tumour tissue.</jats:sec><jats:sec><jats:title>Results</jats:title>One <jats:italic>BRAF</jats:italic>, two <jats:italic>EGFR</jats:italic> TK domain (c.2590G&gt;A, p.864A&gt;T) and 11 <jats:italic>T</jats:italic><jats:italic>P53</jats:italic>, but no <jats:italic>PIK3CA</jats:italic> or <jats:italic>KRAS</jats:italic>, mutations were found. No relationship was found between mutation status, immunostaining and mitotane response or survival.</jats:sec><jats:sec><jats:title>Conclusion</jats:title>In conclusion, our data suggest that the role of EGFR tyrosine kinase inhibitors in ACC is limited. Treatment with EGFR monoclonal antibodies on the other hand might be beneficial for a larger group of patients. The possible efficacy of this therapy in ACC should be evaluated in future trials.</jats:sec>
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Type  article-journal
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Year   2013
DOI  10.1530/eje-13-0093
PubMed  23585556
Wikidata  Q38397241
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